Structural status of the int loci in women showing high incidence of breast cancer

Abstract

Mammary carcinomas in certain mice strains are induced following infection by the MMTV. Insertion of MMTV provirus into the int-1 and int-2 loci results in transcriptional activation of these two proto-oncogenes and is thought to be a key step in breast tumorigenesis in mice. A viral etiology for human breast cancers, though proposed several years ago, is far from proven. However, morphological structures resembling Bittner's particles have been observed earlier in about 39% samples of breast tumor and milk sediments of Parsi women. We therefore investigated in the Parsis, the structural integrity of two potential sites of integration (int-1 and int-2) of the hypothetical human mammary tumor virus and have used for this purpose a large number of patient DNA. The results obtained however failed to distinguish any major structural change existing at the int-1 or the int-2 sites that may point to a proviral integration event having occured in human breast cancers. We have, however, observed differences in the physical structure of the int-1 map, compared to the one reported and sequenced, and have therefore felt it necessary to present a new one indicating our findings, notably, the polymorphic PvuII sites. In addition, we report a single case of Parsi woman, with infiltrating grade 3 ductal carcinoma, whose DNA contains an alteration in the int-2 structure.